Opioid Peptides: Peripheral Nervous System

  • Shiro Konishi


As exemplified by the history of research in classical autonomic physiology, synapses in the peripheral nervous system can serve as excellent experimental models for the identification of transmitter substances and the detailed elucidation of mechanisms of chemical transmission. This has been particularly true in the study of signal transmission associated with peptidergic neurons. Until the early 1970s there was firm evidence supporting only two substances, acetylcholine (ACh) and norepinephrine, as neurotransmitters in the mammalian peripheral nervous system. During the past several years, however, a series of studies on vertebrate autonomic neurons, especially in sympathetic ganglia, have provided good evidence that some neuropeptides, including enkephalins, LHRH-like peptide (see Chapter 16), and substance P (see Chapter 13), serve as neurotransmitters for particular forms of synaptic responses, characterized by their relatively long durations, that modulate cholinergic transmission in the ganglia. This chapter reviews experiments aimed at elucidating the neurotransmitter role of opioid peptides and the cellular mechanisms of their actions in the peripheral nervous system.


Enteric Nervous System Opioid Peptide Sympathetic Ganglion Myenteric Neuron Conditioning Stimulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alm, P., Almets, J., Hskanson, R., Owman, Ch., Sjoberg, N. -O., Stjernqvist, M., and Sunder, F., 1981, Enkephalin-immunoreactive nerve fibers in the feline genito-urinary tract, Histochemistry 72: 351–355.PubMedCrossRefGoogle Scholar
  2. Aronin, N., DiFiglia, M., Liotta, A. S., and Martin, J. B., 1981, Ultrastructural localization and biochemical features of immunoreactive Leu-enkephalin in monkey dorsal horn, J. Neurosci. 1: 561–577.PubMedGoogle Scholar
  3. Ashe, J. H., and Libet, B., 1981, Orthodromic production of noncholinergic slow depolarizing response in the superior cervical ganglion of the rabbit, J. Physiol. (Lond.) 320: 333–346.Google Scholar
  4. Barber, R. P., Vaughan, J. E., Slemmon, J. R., Salvaterra, P. M., Roberts, E., and Leeman, S. E., 1979, The origin, distribution and synaptic relationships of substance P axons in rat spinal cord, J. Comp. Neurol. 184: 331–351.PubMedCrossRefGoogle Scholar
  5. Bennett, M. R., and Lavidis, N. A., 1980, An electrophysiological analysis of the effects of morphine on the calcium dependence of neuromuscular transmission in the mouse vas deferens, Br. J. Pharmacol. 69: 185–191.PubMedGoogle Scholar
  6. Bitar, K. N., and Makhlouf, G. M., 1982, Specific opiate receptors on isolated mammalian gastric smooth muscle cells, Nature 297: 72–74.PubMedCrossRefGoogle Scholar
  7. Bixby, J. L., and Spitzer, N. C., 1983, Enkephalin reduces quantal content at the frog neuromuscular junction, Nature 301: 431–432.PubMedCrossRefGoogle Scholar
  8. Björkroth, U., 1983, Inhibition of smooth muscle contractions induced by capsaicin and electrical transmural stimulation by a substance P antagonist, Acta Physiol. Scand. JSuppl. 515: 11–16.Google Scholar
  9. Bornstein, J. C., and Fields, H. L., 1979, Morphine presynaptically inhibits a ganglionic cholinergie synapse, Neurosci. Lett. 15: 77–82.Google Scholar
  10. Burnstock, G., 1981, Neurotransmitters and trophic factors in the autonomic nervous system, J. Physiol. (Lond.) 313: 1–35.Google Scholar
  11. Cooks, T., and Burnstock, G., 1979, Effects of neuronal polypeptides on intestinal smooth muscle: a comparison with nonadrenergic, noncholinergic nerve stimulation and ATP, Eur. J. Pharmacol. 54: 251–259.CrossRefGoogle Scholar
  12. Dalsgaard, C. -J., Hökfelt, T., Elfvin, L. -G., Skirboll, L., and Emson, P., 1982a, Substance P-containing primary sensory neurons projecting to the inferior mesenteric ganglion: Evidence from combined retrograde tracing and immunohistochemistry, Neuroscience 7: 647–654.PubMedCrossRefGoogle Scholar
  13. Dalsgaard, C. -J., Hökfelt, T., Elfyin, L. -G., and Terenius, L., 1982b, Enkephalin-containing sympathetic preganglionic neurons projecting to the inferior mesenteric ganglion: Evidence from combined retrograde tracing and immunohistochemistry, Neuroscience 7: 2039–2050.PubMedCrossRefGoogle Scholar
  14. Del Castillo, J., and Katz, B., 1954, Quantal components of the end-plate potential, J. Physiol. (Lund.) 124: 560–573.Google Scholar
  15. Dennis, M. J., Harris, A. J., and Kuffler, S. W., 1971, Synaptic transmission and its duplication by focally applied acetylcholine in parasympathetic neurons in the heart of the frog, Proc. R. Soc. Lond. Ser. B 177: 509–539.CrossRefGoogle Scholar
  16. Edin, R., Lundberg, J., Terenius, L., Dahlström, A., Hökfelt, T., Kewenter, J., and Ahlman, H., 1980, Evidence for vagal enkephalinergic neural control of the feline pylorus and stomach, Gastroenterology 78: 492–497.PubMedGoogle Scholar
  17. Furness, J. B., Costa, M., and Miller, R. J., 1983, Distribution and projections of nerves with enkephalin-like immunoreactivity in the guinea-pig small intestine, Neuroscience 8: 653–664.PubMedCrossRefGoogle Scholar
  18. Gintzler, A. R., and Scalisi, J. A., 1982, Effects of opioids on non-cholinergic excitatory responses of the guinea-pig isolated ileum: Inhibition of release of enteric substance P, Br. J. Pharmacol. 75: 199–205.PubMedGoogle Scholar
  19. Glazer, E. J., and Basbaum, A. L., 1980, Leucine enkephalin: Localization in and axoplasmic transport by sacral parasympathetic preganglionic neurons, Science 208: 1479–1481.PubMedCrossRefGoogle Scholar
  20. Hartschuh, W., Weihe, E., Buchler, M., Helmstaedter, V., Feurle, G. E., and Forssmann, W. G., 1979, Met-enkephalin-like immunoreactivity in Merkel cells, Cell Tissue Res. 201: 343–348.PubMedCrossRefGoogle Scholar
  21. Hirst, G. D. S., 1979, Mechanisms of peristalsis, Br. Med. Bull. 35: 263–268.PubMedGoogle Scholar
  22. Hughes, J., Kosterlitz, H. K., and Leslie, F. M., 1975, Effect of morphine on adrenergic transmission in the mouse vas deferens. Assessment of agonist and antagonist potencies of narcotic analgesics, Br. J. Pharmacol. 53: 371–381.PubMedGoogle Scholar
  23. Hughes, J., Kosterlitz, H. W., and Smith, T. W., 1977, The distribution of methionine-enkephalin and leucine-enkephalin in the brain and peripheral tissues, Br. J. Pharmacol. 61: 639–647.PubMedGoogle Scholar
  24. Illes, P., Zieglgänsberger, W., and Herz, A., 1980, Calcium reverses the inhibitory action of morphine on neuroeffector transmission in the mouse vas deferens, Brain Res. 191: 511–522.PubMedCrossRefGoogle Scholar
  25. Ito, Y., and Tajima, K., 1980, Action of morphine on the neuroeffector transmission in the guinea-pig ileum and in the mouse vas deferens, J. Physiol. (Lund.) 307: 367–383.Google Scholar
  26. Jessen, K. R., Saffrey, M. J., van Noorden, S., Bloom, S. R., Polak, J. M., and Burnstock, G., 1980, Immunohistochemical studies of the enteric nervous system in tissue culture and in situ: Localization of vasoactive intestinal polypeptide (VIP), substance P and enkephalin immunoreactive nerves in the guinea-pig gut, Neuroscience 5: 1717–1735.PubMedCrossRefGoogle Scholar
  27. Jessell, T. M., and Iversen, L. L., 1977, Opiate analgesics inhibit substance P release from rat trigeminal nucleus, Nature 268: 549–551.PubMedCrossRefGoogle Scholar
  28. Jiang, Z. G., Simmons, M. A., and Dun, N. J., 1982, Enkephalinergic modulation of non-cholinergic transmission in mammalian prevertebral ganglia, Brain Res. 235: 185–191.PubMedCrossRefGoogle Scholar
  29. Katayama, Y., and Nishi, S., 1981, Actions of enkephalin on single neurons in ciliary ganglia, in: Advances in Endogenous and Exogenous Opioids ( H. Takagi and E. J. Simon, eds.), Kodanslia, Tokyo, pp. 205–207.Google Scholar
  30. Katayama, Y., North, R. A., and Williums, J. T., 1979, The action of substance P on neurons of the myenteric plexus of the guinea-pig intestine, Proc. R. Soc. Lond. Ser. B 206: 191–208.CrossRefGoogle Scholar
  31. Kato, K., and Kuba, K., 1980, Inhibition of transmitter release in bullfrog sympathetic ganglia induced by y-aminobutyric acid, J. Physiol. (Lond.) 298: 271–283.Google Scholar
  32. Kondo, H., and Yui, R., 1982, An electron microscopic study on enkephalin-like immunoreactive fibers in the celiac ganglion of guinea-pig, Brain Res. 252: 142–145.PubMedCrossRefGoogle Scholar
  33. Konishi, S., Tsunoo, A., and Otsuka, M., 1979a, Enkephalins presynaptically inhibit cholinergic transmission in sympathetic ganglia, Nature 282: 515–516.PubMedCrossRefGoogle Scholar
  34. Konishi, S., Tsunoo, A., and Otsuka, M., 1979b, Substance P and noncholinergic excitatory synaptic transmission in guinea-pig sympathetic ganglia, Proc. Jpn. Acad. Ser. B. 55: 525–530.CrossRefGoogle Scholar
  35. Konishi, S., Tsunoo, A., Yanaihara, N., and Otsuka, M., 1980, Peptidergic excitatory and inhibitory synapses in mammalian sympathetic ganglia: Roles of substance P and enkephalin, Biomed. Res. 1: 528–536.Google Scholar
  36. Konishi, S., Tsunoo, A., and Otsuka, M., 1981, Enkephalin as a transmitter for presynaptic inhibition in sympathetic ganglia, Nature 294: 80–82.PubMedCrossRefGoogle Scholar
  37. Konishi, S., Otsuka, M., Folkers, K., and Rosell, S., 1983, A substance P antagonist blocks noncholinergic slow excitatory postsynaptic potential in guinea-pig sympathetic ganglia, Acta Physiol. Scand. 117: 157–160.CrossRefGoogle Scholar
  38. Kromer, W., and Pretzlaff, W., 1979, In vitro evidence for the participation of intestinal opioids in the control of peristalsis in the guinea pig small intestine, Naunyn Schmiedebergs Arch. Pharmacol. 309: 153–157.Google Scholar
  39. Kuffler, S. W., 1980, Slow synaptic responses in autonomic ganglia and the pursuit of a peptidergic transmitter, J. Exp. Biol. 89: 257–286.PubMedGoogle Scholar
  40. Libet, B., 1979, Which postsynaptic action of dopamine is mediated by cyclic AMP? Life Sci. 24: 1043–1058.PubMedCrossRefGoogle Scholar
  41. Lord, J. A., Waterfield, A. A., Hughes, J., and Kosterlitz, H. W., 1977, Endogenous opioid peptides: Multiple agonists and receptors, Nature 267: 495–499.PubMedCrossRefGoogle Scholar
  42. Lundberg, J. M., Hökfelt, T., Fahrenkrug, J., Nilsson, G., and Terenius, L., 1979, Peptides in the cat carotid body (glomus caroticum): VIP-, enkephalin-, and substance P-like immunoreactivity, Acta Physiol. Scand. 107: 279–281.CrossRefGoogle Scholar
  43. Lundberg, J. M., Sarfa, A., Brodin, E., Rosell, S., and Folkers, K., 1983, A substance P antagonist inhibits vagally induced increase in vascular permeability and bronchial smooth muscle contraction in the guinea pig, Proc. Natl. Acad. Sci. USA 80: 1120–1124.PubMedCrossRefGoogle Scholar
  44. Macdonald, R. L., and Nelson, P. G., 1978, Specific-opiate-induced depression of transmitter release from dorsal root ganglion cells in culture, Science 199: 1449–1451.PubMedCrossRefGoogle Scholar
  45. Machova, J., and Kvaltinova, Z., 1983, The actions of [Leu’] enkephalin and morphine in cat sympathetic ganglion, Eur. J. Pharmacol. 87: 277–282.PubMedCrossRefGoogle Scholar
  46. Martin, A. R., 1977, Junctional transmission, II. Presynaptic mechanisms, in: Handbook of Physiology, Vol. 1, Cellular Biology of Neurons, Part 1 ( E. R. Kandel, ed.), American Physiological Society, Bethesda, pp. 329–355.Google Scholar
  47. Morita, K., and North, R. A., 1981, Opiate and enkephalin reduce the excitability of neuronal processes, Neuroscience 6: 1943–1951.PubMedCrossRefGoogle Scholar
  48. Morita, K., and North, R. A., 1982, Opiate activation of potassium conductance in myenteric neurons: Inhibition by calcium ion. Brain Res. 242: 145–150.PubMedCrossRefGoogle Scholar
  49. Mudge, A. W., Leeman, S. E., and Fischbach, G. D., 1979, Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration, Proc. Natl. Acad. Sci. USA 76: 526–530.PubMedCrossRefGoogle Scholar
  50. North, R. A., and Williams, J. T., 1983, How do opiates inhibit neurotransmitter release? Trends Pharmacol. Sci. 4: 337–339.Google Scholar
  51. North, R. A., Katayama, Y., and Williams, J. T., 1979, On the mechanism and site of action of enkephalin on single myenteric neurons, Brain Res. 165: 67–77.PubMedCrossRefGoogle Scholar
  52. Otsuka, M., and Konishi, S., 1983, Substance P-the first peptide neurotransmitter? Trends Neurosci. 6: 317–320.CrossRefGoogle Scholar
  53. Paton, W. D. M., 1957, The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea-pig ileum, Br. J. Pharmacol. 12: 119–127.Google Scholar
  54. Paterson, S. J., Robson, L. E., and Kosterlitz, H. W., 1983, Classification of opioid receptors, Br. Med. Bull. 39: 31–36.PubMedGoogle Scholar
  55. Puig, M. M., Gascon, P., Craviso, G. L., and Musacchio, J. M., 1977, Endogenous opiate receptor ligand: Electrically induced release in the guinea pig ileum, Science 195: 419–420.PubMedCrossRefGoogle Scholar
  56. Sakai, K. K., Hymson, D. L., and Shapiro, R., 1978, The mode of action of enkephalins in the guinea-pig myenteric plexus, Neurosci. Lett. 10: 317–322.Google Scholar
  57. Schultzberg, M., Hökfelt, T., Terenius, L., Elfyin, L. -G., Lundberg, J. M., Brandt, J., Elde, R. P., and Goldstein, M., 1979, Enkephalin immunoreactive nerve fibers and cell bodies in sympathetic ganglia of the guinea-pig and rat, Neuroscience 4: 249–270.PubMedCrossRefGoogle Scholar
  58. Schultzberg, M., Hökfelt, T., Nilsson, G., Terenius, L., Rehfeeld, J. F., Brown, M., Elde, R., Goldstein, M., and Said, S., 1980, Distribution of peptide-, and catecholamine-containing neurons in the gastro-intestinal tract of rat and guinea-pig: Immunohistochemical studies with antisera to substance P, vasoactive intestinal polypeptide, enkephalins, somatostatin, gastrinlcholecystokinin, neurotensin, and dopamine ß-hydroxylase, Neuroscience 5: 689–744.PubMedCrossRefGoogle Scholar
  59. Tokimasa, T., Morita, K., and North, A., 1981, Opiates and clonidine prolong calcium-dependent afterhyperpolarizations, Nature 294: 162–163.PubMedCrossRefGoogle Scholar
  60. Tsunoo, A., Konishi, S., and Otsuka, M., 1982, Substance P as an excitatory transmitter of primary afferent neurons in guinea-pig sympathetic ganglia, Neuroscience 7: 2025–2037.PubMedCrossRefGoogle Scholar
  61. Udenfriend, S., and Kilpatrick, D., 1983, Biochemistry of the enkephalins and enkephalincontaining peptides, Arch. Biochem. Biophys. 221: 309–323.CrossRefGoogle Scholar
  62. Waterfield, A. A., Smockum, R. W. J., Hughes, J., Kosterlitz, H. W., and Henderson, G., 1977, In vitro pharmacology of the opioid peptides, enkephalins and endorphins, Eur. J. Pharmacol. 43: 107–116.PubMedCrossRefGoogle Scholar
  63. Werz, M. A., and Macdonald, R. L., 1982, Heterogeneous sensitivity of cultured dorsal root ganglion neurones to opioid peptides selective for µ- and 8-opiate receptors, Nature 299: 730–733.PubMedCrossRefGoogle Scholar
  64. Wouters, W., and van den Bercken, J., 1980, Effects of met-enkephalin on slow synaptic inhibition in frog sympathetic ganglion, Neuropharmacology 19: 237–243.PubMedCrossRefGoogle Scholar
  65. Yang, H. -Y. T., Hexum, T., and Costa, E., 1980, Opioid peptides in adrenal gland, Life Sci. 27: 1119–1125.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Shiro Konishi

There are no affiliations available

Personalised recommendations